The minor analgesic, phenacetin, induces severe hepatic necrosis in 3-MC-treated hamsters. Antecedent hepatic glutathione depletion and tissue necrosis appear to be mediated by the metabolic conversion of phenacetin to a chemically reactive species capable of irreversibly binding to target organ protein. Because of the suspected contribution of phenacetin to the pathogenesis of analgesic nephropathy, we have attempted to extrapolate those findings to the kidney but have been unsuccessful thus far in developing an experimental model for phenacetin-induced renal damage.